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Article Dans Une Revue Journal of Biological Chemistry Année : 2002

Kinetic Mechanism of Activation of the Cdk2/Cyclin A Complex

Résumé

Eukaryotic cell cycle progression is controlled by the ordered action of cyclin-dependent kinases, activation of which occurs through the binding of the cyclin to the Cdk followed by phosphorylation of a conserved threonine in the T-loop of the Cdk by Cdk-activating kinase (CAK). Despite our understanding of the structural changes, which occur upon Cdk/cyclin formation and activation, little is known about the dynamics of the molecular events involved. We have characterized the mechanism of Cdk2/cyclin A complex formation and activation at the molecular and dynamic level by rapid kinetics and demonstrate here that it is a two-step process. The first step involves the rapid association between the PSTAIRE helix of Cdk2 and helices 3 and 5 of the cyclin to yield an intermediate complex in which the threonine in the T-loop is not accessible for phosphorylation. Additional contacts between the C-lobe of the Cdk and the N-terminal helix of the cyclin then induce the isomerization of the Cdk into a fully mature form by promoting the exposure of the T-loop for phosphorylation by CAK and the formation of the substrate binding site. This conformational change is selective for the cyclin partner.
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hal-03129145 , version 1 (17-03-2021)

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May Morris, Claire Gondeau, John Tainer, Gilles Divita. Kinetic Mechanism of Activation of the Cdk2/Cyclin A Complex. Journal of Biological Chemistry, 2002, 277 (26), pp.23847-23853. ⟨10.1074/jbc.M107890200⟩. ⟨hal-03129145⟩
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